Non-nmda Receptor-dependent Ltp In Lead Damage Mechanisms And The Role Of Jnk1 In The Synaptic Plasticity In The Hippocampal Ca1 Region

In this paper, using slice patchclamp technique, confocal, hippocampus slice and western bloting techniques, we studied the contribution of ryanodine sensitive stores to impairment of lead (Pb) on NMDA receptor-independent LTP in rat hippocampal CAl neurons; and investigated the role of JNK1 in synaptic plasticity of hippocampal area CA1.1. Lead exposure is known to be associated with cognitive dysfunction in children. Impairment of the induction of long-term potentiation (LTP) has been reported in area CAl of rat hippocampus following lead exposure in vivo and in vitro. The present study was carried out to investigate whether the alterations of N-methyl-D-aspartate (NMDA) receptor-independent LTP following lead exposure involve internal calcium stores in hippocampus CA1 synapses. Monosynaptic field excitatory postsynaptic potentials in hippocampal slice area CAl were recorded using the whole-cell patch-clamp upon acute lead treatment, and these studies were coupled with calcium imaging experiments to observe internal calcium changes in cultured hippocampal neurons. Inhibiting calcium release by ryanodine significantly reduced NMDA receptor-independent LTP, and depletion of internal calcium stores with thapsigargin blocked this form of LTP. Caffeine, an agonist of ryanodine receptors, enhanced this form of LTP. However, caffeine-enhanced NMDA receptorindependent LTP was depressed after bath application of lead. Moreover, lead further decreased ryanodine- and thapsigargin-reduced NMDA receptor-independent LTP. Calcium imaging also confirmed that lead had an effect on internal calcium release and uptake. Taken together, these results demonstrated that lead inhibited NMDA receptor-independent LTP by action on calcium release and uptake by ryanodine-sensitive stores in rat hippocampal area CA1.2. c-Jun N-terminal kinases (JNKs) are stress-activated protein kinases that have been implicated in brain development and are thought to be involved in neuronal apoptosis. Although the function of the JNKs in long-term potentiation (LTP) at hippocampal synapses has been well described recently, relatively little is known about the importance of the JNK1 isoform in synaptic plasticity. Here we showed that, in JNK1 deficient mice, short-term synaptic plasticity was altered. These mice showed normal LTP in response to...